Arthritis, an inflammatory disease of the joint, occurs in various forms such as rheumatoid arthritis and related diseases with joint inflammation.
Rheumatoid arthritis, also called chronic rheumatism, in particular, is a chronic multiple arthritis characterized by inflammatory changes in the synovial membrane of the articular capsule inner layer. Arthritic diseases like rheumatoid arthritis are progressive and cause joint disorders such as deformation and acampsia, often resulting in severe physical disorder due to a lack of effective treatment and subsequent deterioration.
Traditionally, these forms of arthritis have been chemotherapeutically treated with various drugs including steroids and other adrenocortical hormones (e.g., cortisone), non-steroidal anti-inflammatory drugs (e.g., aspirin, piroxicam, indomethacin), gold-containing drugs (e.g., auro-thiomalate), antirheumatic drugs (e.g., chloroquine preparations, D-penicillamine), anti-gout drugs (e.g., colchicine) and immunosuppressors (e.g., cyclophosphamide, azathioprine, methotrexate, levamisole).
However, these drugs have drawbacks such as severe adverse reactions, adverse reactions hampering the drug's long-term use, a lack of efficacy and a failure to be effective against already-occurring arthritis.
Accordingly, there is a need for the development of a drug which exhibits excellent prophylactic/therapeutic action on arthritis with low toxicity in clinical situations.
Heretofore, various compounds have been synthesized as thieno[2,3-b]pyridine derivatives including those described in the Bulletin of the Chemical Society of Japan, Vol. 61, p. 4431 (1988), Chemical and Pharmaceutical Bulletin, Vol. 36, p. 4389 (1988), Phosphorus, Sulfur and Silicon, Vol. 73, p. 127 (1992), Chemical and Pharmaceutical Bulletin, Vol. 40, p. 1376 (1992) and Khim Geterotsikl Soedin, Vol. 1, p. 124 (1987). However, these compounds are limited to the structure in which the substituent at the 6-position in the thieno[2,3-b]pyridine skeleton is a methyl group. Also, no description of anti-inflammatory action, bone resorption inhibitory action or immunosuppressant action is given for these known thienopyridine derivatives.